Advanced Non-small Cell Lung Cancer
Conditions
Interventions
Cohort A:mRNA personalized tumor vaccine encoding neoantigen + toripalimab injection
Cohort B:mRNA personalized tumor vaccine encoding neoantigen + toripalimab injection
Sponsors
Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients aged > 18 years, and the gender is not limited; 2. Patients with non-small cell lung cancer confirmed by histopathology or cytology, who have failed standard treatment, or have no standard treatment plan, or are not suitable for standard treatment at this stage, and have at least one measurable lesion; 3. Fresh biopsy specimens for vaccine preparation can be provided; 4. (1) Cohort A: Non-small cell lung cancer patients with secondary drug resistance after PD-1/PD-L1 drug therapy (The first dose of toripalimab in this trial was >= 6 months from the last PD-1/PD-L1 drug administration); (2) Cohort B: patients who are not PD-L1-positive and non-small cell lung cancer patients who have not been treated with PD-1/PD-L1 drugs; 5. Eastern Cooperative Oncology Group Performance Status Score (ECOG PS) of 0 or 1; 6. Having adequate organ and bone marrow function, as defined below: (1) Blood routine: absolute neutrophil count (ANC) >=1.5x109/L; platelet count (PLT) >=75x109/L; hemoglobin content (HGB) >=9.0 g/dL. No use of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion and platelet transfusion within 14 days before the examination; (2) Liver function: patients without liver metastases require serum total bilirubin (TBIL) <= 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN. Requirements for patients with liver metastases: TBIL<=1.5xULN; ALT and AST<=5xULN; (3) Renal function: serum creatinine (Scr)<=1.5xULN; (4) Adequate coagulation function, defined as international normalized ratio (INR) <= 1.5 or prothrombin time (PT) <= 1.5xULN; if the patient is receiving anticoagulation therapy, as long as the PT is within the proposed range of anticoagulant drugs; 7. Sign the written informed consent, and be able to comply with the visits and related procedures specified in the plan; 8. Eligible patients (male and female) of childbearing potential must agree to use a reliable method of contraception (hormonal or barrier method or abstinence) during the trial and for at least 90 days after the last dose; female patients of childbearing potential must have a negative blood or urine pregnancy test within 7 days prior to the first dose.
Exclusion criteria
Exclusion criteria: 1. Known to be allergic to any tumor vaccine and toripalimab preparation components; or to have had severe allergic reactions to other monoclonal antibodies in the past; 2. Those who are breastfeeding; 3. The expected survival period is less than 3 months; 4. Those who have undergone major surgery or significant trauma within 4 weeks before the first blood collection during the screening period, or are expected to need major surgery during the study period; 5. Received chemotherapy, biological therapy, endocrine therapy, immunotherapy and other anti-tumor drugs within 4 weeks before the first administration, except for the following: (1) Nitrosoureas or mitomycin C within 6 weeks before the first use of the study drug; (2) Oral fluorouracil and small molecule targeted drugs are 2 weeks before the first use of the study drug or within 5 half-lives of the drug (whichever is longer); (3) Chinese patent medicines with anti-tumor indications are within 2 weeks before the first use of the study drug; 6. Those who have received cell therapy in the past; 7. Participating in another interventional clinical study; 8. Central nervous system metastasis or meningeal metastasis with clinical symptoms, or there is other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, and is judged by the investigator to be unsuitable for enrollment; 9. The adverse reactions of previous anti-tumor therapy have not recovered to NCI CTCAE v5.0 grade evaluation the lower limit of the detection value of the research center), preventive antiviral treatment other than interferon is allowed; hepatitis C virus infection; 15. Patients with a history of organ transplantation or waiting for organ transplantation; 16. Any uncontrollable active infection; 17. Immunosuppressed patients, including those with known immunodeficiency; those currently using systemic steroids (except for recent or current use of inhaled steroids); 18. Skin diseases (such as psoriasis) that may prevent intradermal vaccines from entering the target area; 19. The investigators assess that the patients are unable or unwilling to comply with the requirements of the research protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Specific CD4+ and CD8+ T lymphocyte responses against neoantigens induced by mRNA personalized tumor vaccines; | — |
Countries
China
Contacts
Public ContactZhou Caicun
Shanghai Pulmonary Hospital
Outcome results
None listed